Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium.
BACKGROUND
Tachycardia-induced atrial remodelling (as an equivalent to atrial fibrillation) can be influenced by the renin-angiotensin system. Effects of a seven-day enalapril pre-treatment (EPT, 0.16 mg/kg body weight subcutaneously every 24 h) on ionic currents underlying tachycardia-induced early electrical remodelling after 24 h rapid atrial pacing (RAP, 600 beats/min) in rabbit atrium were studied.


METHODS
Animals were divided into four groups (n=4 each): control; paced only; enalapril only; and enalapril and paced, respectively. Using patch-clamp technique in whole-cell mode, current densities were measured in isolated atrial myocytes.


RESULTS
EPT nearly doubled L-type calcium current (ICa,L, -7.7+/-0.6 pA/pF [control] vs. f -12.3+/-1.2 pA/pF [enalapril only]). RAP reduced ICa,L to -3.6+/-0.7 pA/pF (paced only). Also after EPT, RAP led to a significant downregulation of ICa,L by 39% (-7.5+/-1.3 pA/pF [paced and enalapril]). RAP decreased transient outward potassium current (Ito, -45%, 51.5+/-3.9 pA/pF [control] vs. 28.5+/-4.5 pA/pF [paced only]). EPT did not alter Ito (44.2+/-8.1 pA/pF [enalapril only]). However, RAP did not affect Ito in enalapril-treated animals and averaged 50.4+/-9.8 pA/pF (paced and enalapril).


CONCLUSIONS
In summary, EPT has several effects on ion channels in rabbit atrium: 1) EPT increases ICa,L current density, but cannot prevent its downregulation due to RAP; 2) EPT has no influence on Ito current density, but can prevent its downregulation due to RAP. Although changes of single ion channels must be interpreted in context of the complex atrial electrophysiology as a whole, our results provide a possible explanation of the in vivo observation that angiotensin-converting enzyme inhibition is mainly beneficial on the early electrical remodelling due to the atrial fibrillation-equivalent RAP.
Laszlo
Roman
R
Department of Cardiology, University of Tübingen, Germany. roman.laszlo@med.uni
Eick
Christian
C
Rueb
Norman
N
Weretka
Slawomir
S
Weig
Hans-Joerg
HJ
Schreieck
Juergen
J
Bosch
Ralph F
RF
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D004553:Electric Conductivity; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism; D011817:Rabbits; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D013610:Tachycardia / Q000503:physiopathology*
D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D004656:Enalapril